[unreadable] Using several different approaches, the specificity of guanidinoglycoside binding to structured RNAs will be thoroughly explored. During the first year, the development of parallel binding assays for two diverse RNA targets known to bind aminoglycosides will be developed. This will allow the rapid assessment of the binding specificity of guanidinoglycoside derivatives. The next half year of this project will focus on the attachment of nucleobases to guanidinoglycosides in an attempt to confer a sequence-specific interaction with a desired target. This approach will potentially increase the ability of a guanidinoglycoside to distinguish among different RNA targets. The final half of this project will involve the development of conformationally constrained guanidinoglycosides. By reducing the flexibility around glycosidic linkages, the conformational promiscuity of guanidinoglycosides could be reduced, increasing specificity and, potentially, affinity. Using these three specific aims, we will gain a better understanding of how guanidinoglycoside could be engineered to achieve RNA specificity. [unreadable] [unreadable]